Primary hyperoxaluria (PH) is a hereditary disorder (passed from one generation to the next) characterised by excessive urinary excretion of a chemical known as oxalate. The condition causes a special type of oxalate-containing stone to form in the kidney. Patients with PH develop renal insufficiency early in life and die of uraemia or renal failure in childhood or early adult life. Oxalate can also be deposited in the heart, the walls of arteries and veins, blocking their normal function. It can also accumulate in the bones, kidneys and in urogenital tract of men.

PH is a genetic, autosomal recessive condition. It can be passed to a person regardless of gender, only if both his or her parents carry the genetic information for PH. PH is classified as type-I or type-II hyperoxaluria. Both PH types are essentially deficiencies of enzymes, proteins that speed-up (catalyse) chemical reactions in the body. In patients with type-I hyperoxaluria, the liver-specific enzyme pyridoxal-phosphate-dependent enzyme alanine-glyoxylate aminotransferase (AGT) is missing. Type-II hyperoxaluria is caused by low or absent activity of the enzyme glyoxylate reductase (GR). Primary hyperoxaluria is a chronically debilitating and life-threatening condition.

At the time of designation, primary hyperoxaluria affected less than 1 in 10,000 people in the European Union (EU). This is equivalent to a total of fewer than 47,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 468,900,000 (Eurostat 2006).

No satisfactory methods exist that were authorised at the time of application. Taking a lot of fluid is recommended to maintain high production of urine. Combined liver and kidney transplantation could be an option in young children.

Oxalobacter formigenes is a bacterium able to degrade oxalate, the chemical that accumulates in PH. This micro-organism is a part of the normal gut flora and depends on oxalate, as it is its energy source. The human HC-1 strain selected for use is capable of growing in the gut and degrading high amounts of oxalate from food. It is expected that these bacteria will be able to break down oxalate in the gut and they might be able to reduce it from the kidneys, urine and blood.

The effects of Oxalobacter formigenes strain HC-1 have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with primary hyperoxaluria were ongoing.

Oxalobacter formigenes strain HC-1 was not authorised anywhere worldwide for the treatment of primary hyperoxaluria or designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 January 2006 recommending the granting of this designation.

the existence of alternative methods of diagnosis, prevention or treatment;

either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.